Infective Encocarditis Management in the Era of Intravascular Devices
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Infective Endocarditis Jennifer L. Calagan PhD, MD COL MC Cardiology Service
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IE: More than a nostalgic disease. “One of the most serious of all infections.”* Is uniformly fatal if untreated. Continues to have a high case fatality rate even in antibiotic era. 4th leading cause of life-threatening ID. Incidence is increasing. * Pathologic Basis of Disease. Cotran, Kumar, Robbins. 4th Ed.
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Terminology: SBE, IE, ABE, NVE, NBTE, or PVE? “Infectious endocarditis” now preferred… subacute vs. acute is arbitrary and antiquated. etiology may be fungal, bacterial, possibly viral “Infectious” differentiates from marantic, verrucous, rheumatic, etc.
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Epidemiology Exact incidence difficult to measure. Estimated at 0.16 - 5.4 cases/1000 admissions. Is increasing as the at-risk population grows. Age distribution is changing. mean age of patient is up to 55 years. Male:Female = 2-9:1 Uncommon in pregnancy
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Epidemiology Severe kidney disease Diabetes IVs or skin disease (skin flora) Flossing (borderline) (dental flora) Not most procedures
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Predisposing Conditions Strom BL, Abrutyn E, Berlin JA, Kinman JL, Feldman RS, Stolley PD, et al. Ann Intern Med. 1998;129:761-9. IV drug users and nosocomial cases excluded.
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Nonbacterial Thrombotic Endocarditis Sterile platelet-fibrin deposits Occur at sites of eddy currents or jet streams created by pre-existing cardiac disease Create the “soil” for bacterial deposition. Characteristically, non-inflammatory
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Infection Growth of vegetation by platelet-fibrin deposition yields a sanctuary for bacteria.
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Microbiology sx’s<60 d post op
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Streptococci in IE
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Viridans Streptococci 30-65% of native valve endocarditis Normal oral commensals A group, composed of several species: S. mitior, S. sanguis, S. mutans,etc. Alpha-hemolytic, non-typable Typical agents of classic “SBE” Strep. viridans
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Other Streptococci S. bovis Lancefield group D Gut flora: associated with GI pathology S. pneumonia 1-3% of cases of IE with predilection for AV Usually, in those with immune suppression DM and Ethanolism Group B Streptococci Elderly with chronic disease
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Enterococcus Normal inhabitant of GI tract. Frequently encountered in UTIs. Up to 40% of cases without identified underlying predisposition to IE. Difficult to treat due to drug resistance.
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Staphylococci Coagulase Positive (Staph. aureus) a major causative agent in all populations of IE typically produces “acute” IE fulminant, rapidly progressive with few immunologic signs. CNS complications in 30-50% Coagulase Negative (Staph. epi, et al) Major cause of PVE. 3-8% of NVE.
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HACEK organisms Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella Gram negative inhabitants of the upper airways. Large vegetations, high likelihood of embolization. Slow growing: hold cultures for 3 weeks. Traditionally sensitive to beta lactams, now some produce beta lactamase.
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Fungi Commonly encountered agents: Candida, Torulopsis, Aspergillus Predispositions Prosthetic valves IVDA Immunosupression Hyperalimentation Prolonged abx treatment Large vegetations and frequent embolic events.
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Other Organisms Pseudomonas Brucella Diphtheroids Listeria Bartonella Coxsiella Chlamydia
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IV Drug Users Accounts for 25% of cases of IE in US. 5:1 male:female Pre-existing valvular diseases uncommon. Variable microbiology. Mortality<10%.
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Prosthetic Valve IE Affects 3% of prosthesis patients. Highest risk in first 6 months post op. Accounts for 10-20% of all IE cases. Increased risk in… Males Blacks Prolonged pump time Multiple valve replacement
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Prosthetic Valve IE “Early” (<2 months)-Staph epi “late” (after 2 months)- mimics NVE
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Peripheral Manifestations Janeway Lesions: erythematous, macular, non tender. septic emboli? Osler’s Nodes: Tender, subcutaneous nodules. 4 P’s: Pink Painful Pea-sized Pulp of the fingers/toes. Immunologic origin?
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Bleeding Subungual (splinter) hemorrhage Conjunctival hemorrhage Retinal hemorrhage: Roth Spot
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Lab Investigations Anemia of Chronic Disease in 50-80% ESR “almost always” elevated. May be normal in those with CHF. Urinalysis gross or microscopic hematuria casts in glomerulonephritis bacteriuria and pyuria Elevated BUN and Creatinine Rheumatoid factor present in 50%
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Diagnosis Frequently difficult to diagnose with certainty. Highly variable and often non-specific presentation. Overdiagnosis and Underdiagnosis are common.
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Diagnosis Classic Clinical Approach: Von Reyn (Beth Israel) Criteria Limitations: No Use of Echo. IVDA not identified as a predisposition Lacks sensitivity for “acute” cases. Incorporation of Echo: Durack (Duke) Criteria Increases proportion of definite diagnoses.
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Diagnosis-Duke Criteria Major: Persistently positive blood cultures Typical organisms for IE Persistent bacteremia Evidence of endocardial involvement Positive ECHO New valvular regurgitation
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Diagnosis-Duke Criteria Minor: Predisposing heart condition Fever Vascular phenomena Immunologic phenomena Positive BC (not meeting major) Positive ECHO (not meeting major)
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Diagnosis-Duke Criteria “Definite”: pathologic diagnosis Micro-organisms or Pathologic lesion (confirmed by histology) clinical diagnosis 2 major criteria or 1 major criterion plus 3 minor criteria or 5 minor criteria
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Diagnosis-Duke Criteria “Probable”: Findings consistent with endocarditis but fall short of definite and not rejected “Rejected” Firm alternate diagnosis for manifestations or resolution of manifestations <= 4 days antibiotics or No pathologic evidence of IE at surgery or autopsy after 4 days therapy
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“Echo should be done in all cases of suspected endocarditis.” (This is not all patients with fever or positive blood cultures). Circulation 1997; 95: 1686-1784
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Use of Echo in Diagnosis of IE Native Valves-ACC Guidelines: Detection/characterization of valvular lesions Detection of vegetations and characterization of lesions in patients with CHD Detection of associated abnormalities Reevaluation studies in complex IE Evaluation of patients with high suspicion of culture-negative IE
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Use of Echo in Diagnosis of IE Prosthetic Valves-ACC Guidelines: Detection/characterization of valvular lesions Detection of associated abnormalities Reevaluation in complex IE Evaluation of suspected IE and negative cultures Evaluation of persistent fever without known source
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Use of Echo in Diagnosis of IE TEE: Prosthetic valves Poor visualization on TTE and high suspicion Detection of associated complications Preoperative Reevaluation in complex IE
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Medical Management Tailor therapy to results of susceptibility testing. Use parenteral drugs. Plan for prolonged courses of abx. Be vigilant for adverse drug effects. Use bactericidal agents. Synergistic combinations are useful. Monitor levels of aminoglycosides.
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Persistent Fever on Appropriate Antibiotics Resistance Abscess: local distant Superinfection Fungus
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Culture Negative Endocarditis Most common cause is recent use of abx. Fastidious organisms Fungal Intracellular agents: Bartonella, chlamdia, viruses. Non-infectious (marantic)
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Anticoagulation “If anticoagulation is indicated for another reason it should be continued. Anticoagulation does not prevent embolization due to IE.” ACC guidelines on Diagnosis and Management of Infective Endocarditis.
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Class I Indications for Surgery Acute AR or MR with heart failure. Acute AR with tachycardia and early closure of the MV. Fungal endocarditis. Annular or aortic abscess. Sinus or aortic aneurysm. Persistent bacteremia and valve dysfunction After 7-10 days of appropriate antibiotics. Circulation. 98(18):1949-1984, 1998
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Other Indications for Surgery Class IIa Recurrent emboli after appropriate abx. Agent with known poor response to abx (GNR) with valve dysfunction. Class IIb Mobile vegetations >10 mm. Class III Early infections of MV that can likely be repaired. Persistent pyrexia and leucocytosis with negative blood cultures. Circulation. 98(18):1949-1984, 1998
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Bayer AS, et al. Circ 98:25, 2936-48. 22/29 Dec 98
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Features of High Risk for Complications Prosthetic cardiac valves Left-sided IE Staphylococcus aureus Fungal IE Prior IE
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Features of High Risk for Complications Prolonged symptoms (>9 months) Cyanotic CHD Pulmonary-to-systemic shunts Poor response to antimicrobial therapy
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Complications Occur in Over Half of All Cases Embolic: CNS and Peripheral Ischemic Hemorrhagic Septic: mycotic aneurysm metastatic abscess Local invasive Conduction abnormalities Valvular dysfunction CHF Glomerulonephritis
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CHF High associated mortality Accounts for 80-90% of IE deaths Leading indication for surgery More common with AV involvement More common with Staph aureus? Surgery is strongly indicated in most cases. In-house death reduced from 51% to 9%. Once CHF develops, surgery should be performed promptly.
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Embolic Events Occurs in 22-50% of cases. 65% of events occur in CNS 90% of these in MCA distribution Associated with high mortality Highest incidence with S. aureus, Candida sp., and HACEK organisms.
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Embolic Events Risk for embolism drops dramatically within two weeks of antibiotic therapy institution. 13 to <1.2 events/1000 patient-days MV disease > AV disease, AML disease the highest. Size of vegetation and embolic potential remain incompletely explained.
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Embolic Events: an Aggressive Approach Clinical Embolic Event (CNS or peripheral) CT/MR of Brain Small, ischemic infarcts & Mild neurologic impairment Vegetations present by echo Prompt Surgery Large or hemorrhagic infarct Observe Blaustein AS Card Clin 14:3,1996
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Mycotic Aneurysm 2-5% of all cerebral aneurysms More common in debilitated patients Suspect when encountered in… Persistent fever Pulsatile mass/erythema in peripheral regions Headache, meningitis, neuro deficit for cerebral Surgery recommended whenever possible.
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Periannular Extension of Infection 10-40% of all NVE AV>TV 56-100% of all PVE annulus is usually the primary site of infection May develop into fistulous tracts or shunts. New AV block has a PPV of 88%. Best diagnosed by TEE. Best surgical option is frequently the homograft. Improved penetration of antibiotics.
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Circulation. 96(1):358-366, 1997 July 1. Prophylaxis
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High Risk: Prophylaxis Recommended Prosthetic cardiac valves, including bioprosthetic and homograft valves Previous bacterial endocarditis Complex cyanotic congenital heart disease (eg, single ventricle states, transposition of the great arteries, tetralogy of Fallot) Surgically constructed systemic pulmonary shunts or conduits
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Moderate Risk: Prophylaxis Recommended Most other congenital cardiac malformations (other than above and below) Acquired valvular dysfunction (eg, rheumatic heart disease) Hypertrophic cardiomyopathy Mitral valve prolapse with valvular regurgitation and/or thickened leaflets
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Low Risk: Prophylaxis Not Recommended Isolated secundum atrial septal defect Surgical repair of atrial septal defect, ventricular septal defect, or patent ductus arteriosus (without residua beyond 6 mo) Previous coronary artery bypass graft surgery Mitral valve prolapse without valvular regurgitation *
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Low Risk: Prophylaxis Not Recommended Physiologic, functional, or innocent heart murmurs Previous Kawasaki disease without valvular dysfunction Previous rheumatic fever without valvular dysfunction Cardiac pacemakers (intravascular and epicardial) and implanted defibrillators
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Prophylaxis Recommended Respiratory Tract Tonsillectomy Violation of respiratory mucosa. Rigid bronchoscopy. Gastrointestinal Tract Esophageal sclerotherapy or stricture dilation ERCP Billiary surgery Violation of intestinal mucosa GU Tract Prostate surgery Cystoscopy Urethral dilatation
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Prophylaxis Not Recommended Respiratory Tract ET intubation Flexible bronchoscopy PE tubes GI Tract TEE EGD
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Prophylaxis Not Recommended GU Tract Vaginal hysterectomy Vaginal delivery C - section In uninfected tissue: D and C/Ab Urethral cath Sterilization IUDs Circumcision
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Infective Endocarditis Questions?
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“The practice of medicine is an art, not a trade; a calling, not a business; a calling in which your heart will be exercised equally with your head. Often the best part of your work will have nothing to do with potions and powders, but with the exercise of an influence of the strong upon the weak, of the righteous upon the wicked, of the wise upon the foolish.” William Osler
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Infective Endocarditis 19 January 1999
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Pathologically Confirmed Cases n=69
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Additional Studies Bayer AS, et al. Circ 98:25, 2936-48. 22/29 Dec 98
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Use of Echo in Diagnosis of IE Bayer AS, et al. Circ 98:25, 2936-48. 22/29 Dec 98
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Management of IE
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The Sanford Guide to Antimicrobial Therapy Gilbert DN, Moellering RC, Sande MA, eds. 28th ed. 1998. Antimicrobial Therapy for IE
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Sanford, et al.
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Sanford, et al.
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Sanford, et al. + gent x 14 d
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Surgery for PVE
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IE Prophylaxis in MVP
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ACC guidelines on Diagnosis and Management. of Infective Endocarditis. Class I Indications for Surg
ACC guidelines on Diagnosis and Management. of Infective Endocarditis. Class I Indications for Surgery. Acute AR or MR with heart failure. ...
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